1. Field of the Invention
This invention relates to an improved process for the production of 4'-isobutylacetophenone (4-IBAP). Various processes are known in which 4-IBAP is used as an intermediate in the production of ibuprofen, a widely used nonsteroidal anti-inflammatory drug which has been converted from ethical, i.e., prescription, to over-the-counter status.
2. Description of Related Art
The following information is disclosed in accordance with the terms of 37 CFR 1.56, 1.97 and 1.98.
U.S. Pat. No. 3,385,886, shows the production of phenylalkane derivatives such as ibuprofen in which the first step of the process is the reaction of a phenylalkane with acetyl chloride in the presence of aluminum chloride to produce an alkylphenylacetophenone.
Japanese Patent Publication (Early Disclosure) No. 60 [1985]-188,343, discloses the preparation of p-isobutylacetophenone by the acetylation of isobutylbenzene using as an acetylating agent acetyl fluoride prepared by reacting acetic anhydride with hydrogen fluoride, and as a catalyst, a combination of hydrogen fluoride and boron trifluoride.
Baddely et al., Journal of the Chemical Society, 4943-4945 [1956], discloses on page 4945 the preparation of 4'-isobutylacetophenone by the Friedel-Crafts acetylation of isobutylbenzene with acetyl chloride using aluminum chloride as a catalyst.
Pending application Ser. No. 158,141 filed Mar. 4, 1988 by Elango et al., shows the production of 4'-isobutylacetophenone (4-IBAP) by the Friedel-Crafts acetylation of isobutylbenzene (IBB) with an acetylating agent which may be acetyl fluoride (AcF) or acetic anhydride (Ac.sub.2 O), using a catalyst which may be hydrogen fluoride. The 4'-isobutylacetophenone is disclosed as an intermediate in a process for the production of ibuprofen.
Parent application Ser. No. 07/445,055 filed Dec. 4, 1989, discloses the operation of an extractor reactor to produce 4IBAP and the removal of HF from the product of the latter operation by reacting the HF with acetic anhydride in an HF removal column, both contemplated under the invention of this application. The entire disclosure of this application is incorporated by reference.